ABT-737对人急性髓细胞白血病细胞U937诱导凋亡作用及机制  

The pro-apoptosis effect of ABT-737 and its mechanism in acute myeloid leukemia cells

作　　者：饶佳[1] 高琳琳[2] RAO Jia;GAO Lin-lin(Department of Health Management,the First Affiliated Hospital of Nanchang University,Nanchang 330006,Jiangxi,China;不详)

机构地区：[1]南昌大学第一附属医院健康管理中心,江西南昌330006 [2]南昌大学第一附属医院血液科,江西南昌330006

出　　处：《广东医学》2020年第10期1000-1004,共5页Guangdong Medical Journal

基　　金：江西省卫健委科技计划项目(20191019)。

摘　　要：目的探讨Bcl-2小分子抑制剂ABT-737对人急性髓细胞白血病细胞U937诱导凋亡作用及机制。方法以人急性髓细胞白血病细胞U937为研究对象,观察不同浓度梯度(0、0.625、1.25、2.5、5.0、10μmol/L)ABT-737对U937细胞增殖抑制及诱导凋亡作用,并检测ABT-737作用前后Bcl-2 mRNA水平和蛋白表达水平改变。CCK-8检测细胞生长抑制率,Annexiin-V/PI双染检测细胞凋亡率,RT-PCR方法检测Bcl-2 mRNA水平,Western blot检测Bcl-2蛋白表达。结果ABT-737可显著抑制U937细胞生长,随着ABT-737浓度(0、0.625、1.25、2.5、5.0、10μmol/L)的增加,U937细胞数量逐渐减少。其中2.5μmol/L ABT-737即可使U937细胞出现明显增殖抑制,作用24 h后其存活率与对照组(0μmol/L)比较差异有统计学意义(P<0.05)。ABT-737可显著诱导U937细胞凋亡,随着ABT-737浓度(0、0.625、1.25、2.5、5.0、10μmol/L)的增加,凋亡率逐渐增加。其中2.5μmol/L ABT-737就能显著诱导U937细胞凋亡,作用24 h后U937细胞凋亡率与对照组(0μmol/L)比较差异有统计学意义(P<0.05)。0、0.625、1.25、2.5、5.0、10μmol/L的ABT-737与U937细胞作用24 h后,U937细胞的Bcl-2 mRNA水平有显著下调作用。0、0.625、1.25、2.5、5.0、10μmol/L的ABT-737与U937细胞作用24 h后,Western blotting结果显示,Bcl-2蛋白表达水平逐渐下降,5.0μmol/L ABT-737作用细胞24 h即可完全抑制Bcl-2蛋白表达。结论ABT-737可通过抑制Bcl-2蛋白表达而诱导U937细胞凋亡。Objective To investigatethe inhibitory effect of ABT-737 on proliferation of acute myeloid leukemia(AML)cells and its mechanism.Methods U937cellswere treated with ABT-737 of different concentrations(0,0.625,1.25,2.5,5.0,10μmol/L).The effect of ABT-737 on cell viability and proliferation was assessedby cck-8.The pro-apoptosis effect of ABT-737 on cell was analyzed by Annexin-V/PI assay.Transcription and expression of Bcl-2 were determined by RT-PCR and western blotting analysis,respectively.Results ABT-737 significantly inhibited proliferation in U937 cells.With the increased concentration of the ABT-737(0、0.625、1.25、2.5、5.0、10μmol/L),there were significant increase in cell growth inhibitory rates.Treated with U937 cells for 24 hours,ABT-737 in 2.5μmol/L concentration can inhibited proliferation in U937 cells.Compared with the control group,the difference was statistically significant(P<0.05).ABT-737 significantly induced apoptosis in U937 cells.With the increased concentration of the ABT-737(0、0.625、1.25、2.5、5.0、10μmol/L),there were significant increase in cell pro-apoptosis rates.Treated with U937 cells for 24 hours,ABT-737 in 2.5μmol/L concentration can induced apoptosis in U937 cells.Compared with the control group,the difference was statistically significant(P<0.05).Treated with different concentration of the ABT-737(0、0.625、1.25、2.5、5.0、10μmol/L)for 24 hours,the Bcl-2 mRNA levels in U937 were significantly down-regulated.Western blotting results show that treated with different concentration of the ABT-737(0、0.625、1.25、2.5、5.0、10μmol/L)for 24 hours,the Bcl-2 protein levels in U937 were significantly down-regulated.ABT-737 in 5.0μmol/L concentration can completely inhibited the expression of Bcl-2 protein.Conclusion ABT-737 induces apoptosis ofU937 cells via down-regulation of Bcl-2.

关 键 词：ABT-737 急性髓细胞白血病 凋亡 

分 类 号：R733.71[医药卫生—肿瘤] R552[医药卫生—临床医学]